Just in time for Valentine's Day: Researchers identify a gene critical for heart function

Feb 04, 2011

Hearts from a wild type control mouse (left) and from a DOT1L-deleted mouse displaying dilated cardiomyopathy (right) . In the absence of DOT1L hearts become severely enlarged, compromising heart function.

(PhysOrg.com) -- Everyone knows chocolate is critical to a happy Valentine's Day. Now scientists are one step closer to knowing what makes a heart happy the rest of the year.

Its a gene called DOT1L, and if you dont have enough of the DOT1L enzyme, you could be at risk for some types of heart disease. These findings from a study led by researchers at the University of North Carolina at Chapel Hill School of Medicine appear in the Feb. 1, 2011 issue of the journal Genes and Development.

The team created a special line of mice that were genetically predisposed to dilated cardiomyopathy, a condition in which the heart expands like a balloon, causing its walls to thin and its pumping ability to weaken. About one in three cases of congestive heart failure is due to dilated cardiomyopathy, a condition that also occurs in children.

These mice lack DOT1L. The big discovery came when the researchers were able to prevent the mice from developing the disease by re-expressing a single downstream target gene, Dystrophin.

We saw this phenotype in the heart and it could be attributed to anywhere between 1 and 1,000 genes. But when we just added back this one gene, the heart function was completely rescued, said the studys lead author, Anh Nguyen, a graduate student in the lab of biochemist Yi Zhang, PhD, at UNCs Lineberger Comprehensive Cancer Center. It was very surprising to us, Nguyen added. Normally youd think youd have to add in a number of genes to really see that effect.

The researchers discovered that the gene depends on the enzyme DOT1L to activate it. If DOT1L levels fall too low, Dystrophin ceases to perform its function, eventually leading to heart disease.

Weve identified a new function of DOT1L, which has been linked to leukemia before, but never linked to heart defects, said Zhang, Kenan Distinguished Professor of biochemistry and biophysics and an Investigator of the Howard Hughes Medical Institute.

Learning how the DOT1L affects Dystrophin could eventually help to improve diagnosis and treatment of patients with dilated cardiomyopathy and other conditions. The more we know about the protein, the better we can use it, Zhang said.

The protein could be a target for gene therapy, for example. If you could manipulate the function of DOT1L, then you could essentially regulate everything else downstream, including Dystrophin or other genes, explained Nguyen.

In addition to their experiments using mice, the team examined samples of human heart tissue. Patients with dilated cardiomyopathy had lower levels of DOT1L than patients with no underlying heart condition, suggesting that the proteins role in humans is similar to its role in mice.

The findings also have potential relevance for Duchenne muscular dystrophy, which is caused by defects in Dystrophin function. About 90% of people with muscular dystrophy develop dilated cardiomyopathy; this study suggests perhaps low levels of DOT1L could be a common factor in both conditions.

Related Stories

During vigorous exercise, heart muscle cells take a beating. In fact, some of those cells rupture, and if not for a repair process capable of resealing cell membranes, those cells would die and cause heart damage (cardiomyopathy).

Researchers at the Burnham Institute for Medical Research (Burnham) have shown in both fruit flies and humans that genes involved in embryonic heart development are also integral to adult heart function. The study, led by ...

Research led by Klaus Stark and Christian Hengstenberg of the University of Regensburg identified a common variant of the cardiovascular heat shock protein gene, HSPB7, which was found to increase risk for dilated cardiomyopathy ...

Researchers in the Heart Institute at Cincinnati Children's Hospital Medical Center have discovered a novel gene responsible for heart muscle disease and chronic heart failure in some children and adults with dilated cardiomyopathy ...

Research using a new mouse model has led to the identification of a potential therapeutic target for a type of leukemia commonly associated with an unfavorable prognosis. The study, published by Cell Press in the November ...

Investigators in The Research Institute at Nationwide Children's Hospital have identified a link between specific modifications of the dystrophin gene and the age of cardiac disease onset in patients with Becker muscular ...

Recommended for you

A team of Yale researchers has developed a simple method that could significantly reduce the time and cost of probing gene expression on a large scale. The findings were published March 2 in the journal Nature Me ...

A new genetic discovery in the field of Huntington's disease (HD) could mean a more effective way in determining severity of this neurological disease when using specific treatments. This study may provide insight for treatments ...

Does the child of a person with a heritable form of cancer have the right to access their parent's genetic information after death? What if no consent was ever established? In the March 2 issue of Trends in Molecular Medicine, biomed ...

Analyzing a puzzling multisystem disorder in three children, genetic experts have identified a new syndrome, shedding light on key biological processes during human development. The research also provides ...

Prostate cells that look normal under the microscope may be hiding genetic mutations that could develop into cancer, prompting new ways to improve treatment for the disease, according to research published ...

In an advance that may potentially lead to new treatments for parasitic hookworms, scientists at the University of Massachusetts Medical School and Cornell University have sequenced the genome of the hookworm, ...

User comments : 0

Please sign in to add a comment.
Registration is free, and takes less than a minute.
Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.

Javascript is currently disabled in your web browser. For full site functionality, it is necessary to enable Javascript.
In order to enable it, please see these instructions.